Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane
- 1 August 2002
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 418 (6901), 988-994
- https://doi.org/10.1038/nature01006
Abstract
Central to the initiation of immune responses is recognition of peptide antigen by T lymphocytes. The cell biology of dendritic cells makes them ideally suited for the essential process of antigen presentation1. Their life cycle includes several stages characterized by distinct functions and mechanisms of regulation2. Immature dendritic cells synthesize large amounts of major histocompatibility complex class II molecules (MHC II), but the αβ-dimers are targeted to late endosomes and lysosomes (often referred to as MHC class II compartments) where they reside unproductively with internalized antigens. After exposure to microbial products or inflammatory mediators, endocytosis is downregulated, the expression of co-stimulatory molecules is enhanced, and newly formed immunogenic MHC II–peptide complexes are transported to the cell surface3,4,5,6,7,8,9,10. That these MHC II molecules reach the surface is surprising, as the lysosomes comprise the terminal degradative compartment of the endocytic pathway from which exogenous components generally cannot be recovered intact11. Here we have visualized this pathway in live dendritic cells by video microscopy, using cells expressing MHC II tagged with green fluorescent protein (GFP). We show that on stimulation, dendritic cells generate tubules from lysosomal compartments that go on to fuse directly with the plasma membrane.Keywords
This publication has 30 references indexed in Scilit:
- Dynamics of Major Histocompatibility Complex Class II Compartments during B Cell Receptor–mediated Cell ActivationThe Journal of Experimental Medicine, 2002
- Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cellsThe Journal of cell biology, 2001
- Transport of Peptide-MHC Class II Complexes in Developing Dendritic CellsScience, 2000
- Imaging Constitutive Exocytosis with Total Internal Reflection Fluorescence MicroscopyThe Journal of cell biology, 2000
- Direct vesicular transport of MHC class II molecules from lysosomal structures to the cell surface.The Journal of cell biology, 1996
- Episomal Vectors Rapidly and Stably Produce High-Titer Recombinant RetrovirusHuman Gene Therapy, 1996
- HLA-DM Is Localized to Conventional and Unconventional MHC Class II–Containing Endocytic CompartmentsImmunity, 1996
- B lymphocytes secrete antigen-presenting vesicles.The Journal of Experimental Medicine, 1996
- Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products.The Journal of Experimental Medicine, 1995
- Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor.The Journal of Experimental Medicine, 1992